Artemisinin Resistance in Plasmodium falciparum Malaria
Arjen M. Dondorp,François Nosten,Poravuth Yi,Debashish Das,Aung Phae Phyo,Joel Tarning,Khin Maung Lwin,Frédéric Ariey,Warunee Hanpithakpong,Sue J. Lee,Pascal Ringwald,Kamolrat Silamut,Mallika Imwong,Kesinee Chotivanich,Pharath Lim,Trent Herdman,Sen Sam An,Shunmay Yeung,Pratap Singhasivanon,Nicholas P. J. Day,Niklas Lindegardh,Duong Socheat,Nicholas J. White +22 more
Reads0
Chats0
TLDR
The overall median clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours in Wang Pha (P<0.001) in each of the two locations as discussed by the authors.Abstract:
We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate–mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P = 0. 31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco–endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.)read more
Citations
More filters
Journal ArticleDOI
Challenges and prospects for dengue and malaria control in Thailand, Southeast Asia
Vincent Corbel,Vincent Corbel,François Nosten,François Nosten,Kanutcharee Thanispong,Christine Luxemburger,Monthathip Kongmee,Theeraphap Chareonviriyaphap +7 more
TL;DR: Despite significant advances in the search for potential dengue vaccines and new therapeutic schemes for malaria, the control of these diseases remains difficult.
Journal ArticleDOI
1H-1,2,3-triazole tethered mono- and bis-ferrocenylchalcone-β-lactam conjugates: synthesis and antimalarial evaluation.
TL;DR: The compound 9f and 9l with N-cyclohexyl substituent proved to be the most potent and non-cytotoxic among the series exhibiting IC50 values of 2.36 and 2.43 μM respectively, against W2 strain of P. falciparum.
Journal ArticleDOI
The Community As the Patient in Malaria-Endemic Areas: Preempting Drug Resistance with Multiple First-Line Therapies.
TL;DR: Maciej F. Boni and colleagues propose deploying multiple first-line combination therapies against malaria within a community to delay drug-resistance evolution.
Journal ArticleDOI
Absence of association between piperaquine in vitro responses and polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe genes in Plasmodium falciparum.
Sébastien Briolant,Maud Henry,Claude Oeuvray,Rémy Amalvict,Eric Baret,Eric Didillon,Christophe Rogier,Bruno Pradines +7 more
TL;DR: The results confirm the interest in and the efficacy of the combination of PPQ and DHA for areas in which parasites are resistant to chloroquine or other quinolines.
Journal ArticleDOI
Past and new challenges for malaria control and elimination: the role of operational research for innovation in designing interventions
Philippe Guyant,Vincent Corbel,Vincent Corbel,Philippe J Guerin,Adeline Lautissier,François Nosten,François Nosten,Sébastien Boyer,Marc Coosemans,Marc Coosemans,Arjen M. Dondorp,Arjen M. Dondorp,Véronique Sinou,Shunmay Yeung,Nicholas J. White,Nicholas J. White +15 more
TL;DR: The threat and the emergency of the artemisinin resistance spread and independent emergence in the GMS was intensely debated as it is now close to the border of India.
References
More filters
Journal ArticleDOI
Evidence of Artemisinin-Resistant Malaria in Western Cambodia
TL;DR: Artemisinins are potent and rapidly acting antimalarial drugs, and their widespread use for treating patients with Plasmodium falciparum malaria raises the question of emerging drug resistance.
Journal ArticleDOI
Artemisinins target the SERCA of Plasmodium falciparum
Ursula Eckstein-Ludwig,Richard Webb,I. D. A. van Goethem,J M East,Anthony G. Lee,Masatsugu Kimura,Paul M. O'Neill,Patrick G. Bray,Stephen A. Ward,Sanjeev Krishna +9 more
TL;DR: It is shown that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor).
Journal ArticleDOI
Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.
TL;DR: Artesunate should become the treatment of choice for severe falciparum malaria in adults because it is more rapidly acting than intravenous quinine in terms of parasite clearance and is simpler to administer.
Journal ArticleDOI
Qinghaosu (artemisinin): the price of success.
TL;DR: Artemisinin combination treatments are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries and a global subsidy would make these drugs more affordable and available.
Journal ArticleDOI
Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.
Ric N. Price,Ric N. Price,Anne-Catrin Uhlemann,Alan Brockman,Rose McGready,Elizabeth A. Ashley,L Phaipun,Rina Patel,Ken Laing,Sornchai Looareesuwan,Nicholas J. White,Nicholas J. White,François Nosten,Sanjeev Krishna +13 more
TL;DR: It is shown that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with mefloquine.
Related Papers (5)
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Frédéric Ariey,Benoit Witkowski,Chanaki Amaratunga,Johann Beghain,Anne-Claire Langlois,Nimol Khim,Saorin Kim,Valentine Duru,Christiane Bouchier,Laurence Ma,Pharath Lim,Rithea Leang,Socheat Duong,Sokunthea Sreng,Seila Suon,Char Meng Chuor,Denis Mey Bout,Sandie Menard,William O. Rogers,Blaise Genton,Thierry Fandeur,Olivo Miotto,Pascal Ringwald,Jacques Le Bras,Antoine Berry,Jean Christophe Barale,Rick M. Fairhurst,Françoise Benoit-Vical,Odile Mercereau-Puijalon,Didier Menard +29 more
Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
Elizabeth A. Ashley,Mehul Dhorda,Rick M. Fairhurst,Chanaki Amaratunga,Pharath Lim,Seila Suon,Sokunthea Sreng,Jennifer M. Anderson,Mao S,Sam B,Chantha Sopha,Char Meng Chuor,Chea Nguon,Siv Sovannaroth,Sasithon Pukrittayakamee,Podjanee Jittamala,Kesinee Chotivanich,K Chutasmit,C Suchatsoonthorn,R Runcharoen,Tran Tinh Hien,Nguyen Thuy-Nhien,Thanh Nv,Nguyen Hoan Phu,Ye Htut,Han Kt,Kyin Hla Aye,Olugbenga A. Mokuolu,Rasaq Olaosebikan,Olaleke Oluwasegun Folaranmi,Mayfong Mayxay,Maniphone Khanthavong,Bouasy Hongvanthong,Paul N. Newton,M A Onyamboko,Caterina I. Fanello,Antoinette Tshefu,Neelima Mishra,Neena Valecha,Aung Pyae Phyo,François Nosten,Yi P,Rupam Tripura,Steffen Borrmann,Mahfudh Bashraheil,Judy Peshu,M A Faiz,Aniruddha Ghose,M A Hossain,Rasheda Samad,M. R. Rahman,Manal Hasan,Ashraful Islam,Olivo Miotto,Roberto Amato,Bronwyn MacInnis,Jim Stalker,Dominic P. Kwiatkowski,Zbynek Bozdech,Atthanee Jeeyapant,Phaik Yeong Cheah,Tharisara Sakulthaew,Jeremy Chalk,Benjamas Intharabut,Kamolrat Silamut,Lee Sj,Benchawan Vihokhern,Chanon Kunasol,Mallika Imwong,Joel Tarning,Taylor Wj,Shunmay Yeung,Charles J. Woodrow,Jennifer A. Flegg,Debashish Das,Jennifer L. Smith,Meera Venkatesan,Christopher V. Plowe,Kasia Stepniewska,Philippe J Guerin,Arjen M. Dondorp,Nicholas P. J. Day,Nicholas J. White +82 more
Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study
Aung Pyae Phyo,Standwell Nkhoma,Kasia Stepniewska,Kasia Stepniewska,Elizabeth A. Ashley,Elizabeth A. Ashley,Shalini Nair,Rose McGready,Rose McGready,Carit Ler Moo,Salma Al-Saai,Arjen M. Dondorp,Arjen M. Dondorp,Khin Maung Lwin,Pratap Singhasivanon,Nicholas P. J. Day,Nicholas P. J. Day,Nicholas J. White,Nicholas J. White,Tim J. Anderson,François Nosten,François Nosten +21 more